Hepatocyte nuclear factor (HNF)-4gamma (NR2A2) is a member of the nuclear receptor super family. These transcription factors regulate diverse physiological processes such as reproduction, development and metabolism. HNF-4gamma, is expressed in adult pancreatic beta cells, kidney, intestine and testis. However, its specific role in regulating gene expression in these tissues is poorly understood. The observation that mutations in pancreatic beta cell transcription factors can cause diabetes mellitus raises the possibility that HNF-4gamma, may be a diabetes gene. Thus, we propose to determine the normal function of HNF-4gamma by studying the phenotype of mice in which this transcription factor has been "knocked out" (both total and conditional) or over expressed (transgenics) in specific tissues such as pancreatic beta cells. These studies will provide a better understanding of the function of HNF-4gamma in health and disease.